User:Eliška Koutná/Sandbox 3
From Proteopedia
Prions
Protein structureThe PrPSc differs from PrPC solely in conformation and is its isoform. The mature PrPC consists of approx. 208 amino acids, arranged as a disordered N-terminus and a globular C-terminal domain consisting of three α-helices and a short, antiparallel β-pleated sheet [1][2]. There is a GPI membrane anchor at the C-terminus that tethers the protein to cell membranes and proteins that are secreted and lacking the anchor component has been proven to be unaffected by the infectious isoform [3]. In contrast to the natural form of prion protein with only about 3 % of β-sheet secondary structure, the PrPSc form has about 47 % of the secondary structure in β-sheets [4] that create a core of four-rung β-solenoid fold [5]. Accordingly, they also differ in their properties. PrPC is soluble, has a life-span between 2 and 4 hours, and is sensitive to proteolytic cleavage – when exposed to proteases, the protein is degraded completely [4]. The two most important cleavage events are the α cleavage which removes the unstructured N-terminal tail and leaves the globular domain attached to the cell membrane, and the cleavage on the C-terminal end (termed PrPC shedding) which releases PrPC into the extracellular space [6]. Under the same conditions, PrPSc is hydrolysed by proteases only partially by forming resistant core fragment PrP 27-30 [4]. In addition, it is insoluble in detergents and has a very long half-life, therefore accumulates in tissues easily. It has a tendency to form aggregates and fibrillar structures and is generally susceptible to oligomerization, whereas the PrPC form mainly exist as a monomer [7]. Monomeric PrPSc has never been isolated. References
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